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Biomedical subjects

Y Aoki

Publications and source records attributed to Y Aoki.

At least 199 records · Page 11Linked to original sources
PubMed1999

Angiogenesis and hematopoiesis induced by Kaposi's sarcoma-associated herpesvirus-encoded interleukin-6.

Kaposi's sarcoma-associated herpesvirus (KSHV; also known as human herpesvirus 8 [HHV-8]) is a herpesvirus linked to the development of Kaposi's sarcoma (KS), primary effusion lymphoma, and a proportion of Castleman's disease. KSHV encodes viral interleukin-6 (vIL-6), which is structurally homologous to human and murine IL-6. The biological activities of vIL-6 are largely unknown. To gain insight into the biology of vIL-6, we expressed vIL-6 in murine fibroblasts NIH3T3 cells and inoculated stable vIL-6-producing clones into athymic mice. vIL-6 was detected selectively in the blood of mice injected with vIL-6-expressing clones. Compared with controls, vIL-6-positive mice displayed increased hematopoiesis in the myeloid, erythroid, and megakaryocytic lineages; plasmacytosis in spleen and lymph nodes; hepatosplenomegaly; and polyclonal hypergammaglobulinemia. vIL-6-expressing NIH3T3 cells gave rise to tumors more rapidly than did control cells, and vIL-6-positive tumors were more vascularized than controls. Vascular endothelial growth factor (VEGF) was detected at higher levels in the culture supernatant of vIL-6-expressing cells compared with controls, and immunohistochemical staining detected VEGF in spleen, lymph nodes, and tumor tissues from mice bearing vIL-6-producing tumors but not control tumors. Thus, vIL-6 is a multifunctional cytokine that promotes hematopoiesis, plasmacytosis, and angiogenesis. Through these functions, vIL-6 may play an important role in the pathogenesis of certain KSHV-associated disorders.

3T3 Cells↗
PubMed1999

Immunosuppressant PG490 (triptolide) inhibits T-cell interleukin-2 expression at the level of purine-box/nuclear factor of activated T-cells and NF-kappaB transcriptional activation.

PG490 (triptolide) is a diterpene triepoxide with potent immunosuppressive and antiinflammatory properties. PG490 inhibits interleukin(IL)-2 expression by normal human peripheral blood lymphocytes stimulated with phorbol 12-myristate 13-acetate (PMA) and antibody to CD3 (IC50 of 10 ng/ml), and with PMA and ionomycin (Iono, IC50 of 40 ng/ml). In Jurkat T-cells, PG490 inhibits PMA/Iono-stimulated IL-2 transcription. PG490 inhibits the induction of DNA binding activity at the purine-box/antigen receptor response element (ARRE)/nuclear factor of activated T-cells (NF-AT) target sequence but not at the NF-kappaB site. PG490 can completely inhibit transcriptional activation at the purine-box/ARRE/NF-AT and NF-kappaB target DNA sequences triggered by all stimuli examined (PMA, PMA/Iono, tumor necrosis factor-alpha). PG490 also inhibits PMA-stimulated activation of a chimeric transcription factor in which the C-terminal TA1 transactivation domain of NF-kappaB p65 is fused to the DNA binding domain of GAL4. In 16HBE human bronchial epithelial cells, IL-8 expression is regulated predominantly by NF-kappaB, and PG490 but not cyclosporin A can completely inhibit expression of IL-8. The mechanism of PG490 inhibition of cytokine gene expression differs from cyclosporin A and involves nuclear inhibition of transcriptional activation of NF-kappaB and the purine-box regulator operating at the ARRE/NF-AT site at a step after specific DNA binding.

Binding Sites↗
PubMed1999

Development of novel cationic liposomes for efficient gene transfer into peritoneal disseminated tumor.

A novel series of cationic lipids has been found, by in vivo screening, to be effective for gene transfer into peritoneal disseminated tumor. O,O'-Ditetradecanoyl-N-(alpha-trimethylammonioacetyl)diethan olamine chloride (DC-6-14), having dimyristyl acid, has shown the highest transfection activity in vitro, provided that 10% fetal bovine serum is present. To enhance the transfection efficiency of DC-6-14, we added dioleoylphosphatidylethanolamine (DOPE) and/or cholesterol (Chol) as helper lipids in various ratios. Cationic liposomes containing DC-6-14, DOPE, and Chol in molar ratios of 1:0.75:0.75 and 1:1:0.8 maintained efficient transfection activity under serum-containing conditions in HRA, mEIIL, and ES-2 cell lines in vitro, as determined by luciferase assay. With our novel liposomes, transfection efficiencies were higher in cells proliferating faster than in cells proliferating slower, depending on mitotic activity as represented by labeling index. In the mEIIL peritoneal disseminated tumor model, cancer cells were specifically transfected with the lacZ gene. Gene transfer was observed by X-Gal staining not only in floating cancer cells in the ascites, but also in the peritoneal disseminated cancer tissue. The percentage of LacZ-positive cells was about 1%, which was significantly higher than with commercially available Lipofectin (0.38%), LipofectACE (0.62%), or LipofectAMINE (0.23%). In the mEIIL peritoneal disseminated tumor-nude mouse model, herpes simplex thymidine kinase gene (HSV tk) transfer with our novel liposomes, followed by ganciclovir (GCV) treatment, resulted in significantly longer survival compared with control mice (p < 0.05, Cox-Mantel). These results suggest that these liposomes show promise as tools in gene therapy for patients with intraperitoneal disseminated cancer.

Animals↗
PubMed1999

Pyogenic vertebral osteomyelitis caused by Campylobacter fetus subspecies fetus. A case report.

STUDY DESIGN: Clinical observation of a patient. OBJECTIVES: To present the clinical features of an unusual infection of the spine caused by Campylobacter fetus subspecies fetus and to suggest treatment. SUMMARY OF BACKGROUND DATA: This is only the second reported case of pyogenic vertebral osteomyelitis caused by Campylobacter fetus subspecies fetus. METHODS: A 66-year-old man had pain of the left lower extremity. Radiologic examination revealed an epidural mass associated with destruction of the L5-S1 vertebral bodies. RESULTS: Biopsy of the epidural mass was performed, and culture yielded Campylobacter fetus subspecies fetus. After intravenous antibiotics, oral doxycycline and erythromycin were given for 5 months. At 9 months after antibiotic treatment was completed, the patient's condition was stable. CONCLUSIONS: Prolonged oral administration of doxycycline and erythromycin was curative in this patient.

Aged↗
PubMed1999

Identification of an enhancer element of class Pi glutathione S-transferase gene required for expression by a co-planar polychlorinated biphenyl.

3,3',4,4',5-Pentachlorobiphenyl (PenCB), one of the most toxic co-planar polychlorinated biphenyl congeners, specifically induces class Pi glutathione S-transferase (GSTP1) as well as cytochrome P-450 1A1 in primary cultured rat liver parenchymal cells [Aoki, Matsumoto and Suzuki (1993) FEBS Lett. 333, 114-118]. However, the 5'-flanking sequence of the GSTP1 gene does not contain a xenobiotic responsive element, to which arylhydrocarbon receptor binds. Using a chloramphenicol acetyltransferase assay we demonstrate here that the enhancer termed GSTP1 enhancer I (GPEI) is necessary for the stimulation by PenCB of GSTP1 gene expression in primary cultured rat liver parenchymal cells. GPEI is already known to contain a dyad of PMA responsive element-like elements oriented palindromically. It is suggested that a novel signal transduction pathway activated by PenCB contributes to the stimulation of GSTP1 expression.

Animals↗
PubMed1999

Therapeutic agent for treating dysuria (NC-1800): absolute configuration of the enantiomers.

The absolute configuration of an enantiomer of the title compound, (+/-)-1. fumaric acid salt, was determined by X-ray crystallographic analysis of (+)-1 [salt of (+)-tartaric acid [(+)-2]]. This salt for X-ray crystallographic analysis was prepared by a simple method. The analysis of (+)-1 [salt of (+)-2] showed that this enantiomer has the 5-S and 1-R absolute configuration. The final R and Rw values were 0.0614 and 0.0713, respectively.

Animals↗
PubMed1999

Ovarian metastasis in stage IB and II cervical adenocarcinoma.

We performed the present study to identify those patients with adenocarcinoma of the cervix in whom ovarian preservation might be acceptable. Between January 1971 and December 1996, 82 patients with International Federation of Gynecology and Obstetrics stage IB and II cervical adenocarcinoma and adenosquamous carcinoma, treated by radical hysterectomy, bilateral salpingo-oophorectomy, and pelvic node dissection, were identified. The mean age of the patients was 44.6 years (range 27-72). The incidence of ovarian metastasis was more frequent in stage II (19.0%) than in stage IB disease (2.5%), in which only 1 patient with apparent extrauterine disease at laparotomy had an ovarian metastasis. No patients with up to inner two-thirds of stromal invasion had ovarian metastasis; however, 5 of 24 patients with outer one-third stromal invasion (20.8%) and 4 of 20 with parametrial invasion (20.0%) had ovarian metastasis. A significantly higher incidence of ovarian metastasis was also observed in 5 of 20 cases with lymph node metastasis (25.0%) than in 4 of 62 patients without lymph node metastasis (6.5%). Multivariate analysis, however, found only deep stromal invasion to be an independent risk factor for ovarian metastasis. Although it would be reasonable to conserve normal-appearing ovaries in young women undergoing radical hysterectomy for treatment of stage IB cervical adenocarcinoma and adenosquamous carcinoma, gross intraoperative inspection of the radical hysterectomy specimen may identify deep cervical invasion or extrauterine spread in those who are at increased risk of ovarian metastases.

Adenocarcinoma↗
PubMed1999

Identification and characterization of mutations in patients with holocarboxylase synthetase deficiency.

Holocarboxylase synthetase deficiency (HCS) is an autosomal recessive disorder characterized by metabolic ketoacidosis, abnormal urine organic metabolites, and dermatitis. These symptoms are improved by pharmacological doses of biotin. In this study, we have analyzed seven patients with HCS deficiency found in European and Middle Eastern countries by using reverse transcription/polymerase chain reaction/single-stranded conformation polymorphism and a sequencing analysis. Although we had previously reported that two mutations were frequent in Japanese patients, no frequent mutations were found in the patients analyzed in this study. Seven novel mutations were identified in the cDNA of the patients; these included three missense mutations, two single-base deletions that resulted in a termination codon, a three-base in-frame deletion, and a 68-bp deletion. A new polymorphism C1121T was also identified in four alleles. A transient expression study demonstrated that the HCS activities of three missense mutations and one amino acid deletion were 1%-14% that of wild-type cDNA; in contrast, the activities of the two single-base deletions followed by a termination codon and Asp571Asn were nearly undetectable. These data suggest that a variety of mutations is responsible for decreasing HCS activity and that the aspartate residue at amino acid position 571 may be crucial for the catalytic activity of HCS.

Carbon-Nitrogen Ligases↗
PubMed1999

Complexed prostate-specific antigen and its volume indexes in the detection of prostate cancer.

OBJECTIVES: To evaluate complexed prostate-specific antigen (cPSA), cPSA density (cPSAD), and cPSA adjusted for the transition zone volume (cPSA-TZ) in comparison with the free-to-total PSA ratio (F/T PSA) and free-to-complexed PSA ratio (F/C PSA) as a means of diagnosing prostate cancer. METHODS: Transition zone volume was determined in 137 of 142 men who underwent systematic sextant biopsies and had total PSA (tPSA) values between 4.1 and 10.0 ng/mL. cPSAD and cPSA-TZ were calculated by dividing the cPSA value by the whole prostate volume and the transition zone volume, respectively. RESULTS: Of the 137 men, 23 (16.8%) had prostate cancer. cPSA predicted the biopsy outcome better than tPSA, F/T PSA, or F/C PSA, although the difference was not significant. A cutoff value of 4.1 ng/mL for cPSA provided a specificity of 42% and a sensitivity of 87%. A combination of cPSA and F/C PSA maintained a sensitivity of 83% and gave an increased specificity of 54%. In a subgroup of 65 patients with smaller prostate volumes (less than 45 mL), the diagnostic value of cPSA-TZ was remarkably increased. A cutoff value of 0.31 for cPSA-TZ provided a sensitivity of 93% and a high specificity of 72%. CONCLUSIONS: cPSA was more specific than tPSA and F/T PSA. As a component of F/C PSA, free PSA could provide additional value to cPSA. cPSA-TZ and cPSAD could be better indicators for prostate cancer than cPSA.

Aged↗
PubMed1999

Burn due to misuse of an acetylene gas burner: a case report.

A rare case of deep penetrating burn injury caused by misuse of a high-pressure acetylene burner is reported. A 35 year old man was admitted with second and third degree burns involving the right arm cubital area and a subcutaneous burn on his right arm caused by a high-pressure acetylene gas flame. Early surgical debridement and secondary skin grafting using a preserved subcutaneous vascular network skin graft (PSVNSG) proved effective in this patient. Skin contracture was prevented and function was recovered. The basis of PSVNSG is that the vascular system existing in the graft is used as a permanent vascular system without degeneration. This case shows that, in this kind of burn injury, subcutaneous tissue damage should be suspected and that it is important to perform surgical debridement early after admission.

Accidents, Home↗
PubMed1999

Catecholaminergic neurons in the diencephalon and basal ganglia of SIDS.

The catecholaminergic systems of sudden infant death syndrome victims were examined in the diencephalon and basal ganglia, in addition to the midbrain, pons, and medulla oblongata, using the immuno-histochemical method involving tyrosine hydroxylase. A significant decrease in tyrosine hydroxylase immunoreactivity was demonstrated in the basal ganglia of sudden infant death syndrome victims between 2 to 12 months of age compared with age-matched control subjects. This change in the basal ganglia may be a secondary finding induced by chronic hypoxia or repeated ischemia in sudden infant death syndrome but suggests impairment of the development of the neuronal connection from the brainstem to the upper cardiorespiratory control in sudden infant death syndrome.

Basal Ganglia↗
PubMed1999

Sudden infant death with anomalous origin of the left coronary artery from the pulmonary artery.

Autopsy of a 2-month-old boy revealed an anomalous origin of the left coronary artery from the pulmonary trunk. The endomyocardial fibrosis associated with myocardial ischemia was noted in the left ventricular wall of the enlarged heart. Death was attributed to silent heart failure due to the anomalous left coronary artery. Significant clinical symptoms are generally observed in patients with such anomalies, however, they might cause sudden death in childhood.

Journal Article↗
PubMed1999

Highly metastatic variant of a mouse colon carcinoma cell line, LM17 and its response to GM-CSF gene therapy.

In order to establish a highly metastatic variant of a mouse colon carcinoma cell line (CT26), BALB/c mice were first subcutaneously injected with CT26 cells. Several weeks later, metastatic tumors in lungs were resected, mechanically dispersed into a single cell suspension and cultured in vitro until cells reached confluency. These tumor cells were then subcutaneously injected into new mice. After repeating this procedure five times, a highly lung metastatic cell line, denoted as LM17, has been established. The LM17 cells grow in vitro with or without serum, whereas parental CT26 cells require serum for their growth. The LM17 cells adhere to type I collagen or fibronectin stronger than CT26 cells do. The LM17 cells invade through Matrigel-coated basement membrane in greater number than CT26 cells. By gelatin zymography, LM17 cells showed higher proteinase activity than CT26. Furthermore, subcutaneous injection of irradiated LM17 cells infected with adenovirus harboring mouse GM-CSF gene prevents the growth and lung metastasis of pre-existing subcutaneous tumor. The injection of irradiated GM-CSF-producing LM17 cells after the surgical removal of pre-existing tumor also protected the occurrence of lung metastasis. These results suggest that this highly metastatic LM17 cell line could be useful for analysis of the lung metastatic mechanism and as the mouse GM-CSF gene therapy model.

Adenoviridae↗
PubMed1999

Efficient screening for catalytic antibodies using a short transition-state analog and detailed characterization of selected antibodies.

One of the major obstacles to acquiring catalytic antibodies is that it requires labor-intensive procedures to select catalytic antibodies from huge repertories of antibodies. Here, we selected potential catalytic Abs by utilizing their affinity towards a short transition-state analog which contained only the transition-state structural element, and evaluated in detail its efficiency to enrich catalytic Abs. Hybridoma supernatants elicited against a phosphonate derivative, the TSA1, were screened by a three-step screening process: step 1, ELISA for TSA1-BSA; step 2, ELISA for the short TSA4; and step 3, competitive-inhibition by the short TSA2. Only 22. 8% of positive mAbs from step 1 were found to be catalytic. The rate of catalytic Abs increased to 45.7% using screening steps 1 plus 2, and reached 83.3% using all three screening steps. This clearly suggests that our screening protocol is an efficient method to select potential catalytic Abs. Furthermore, we characterized the properties of both the catalytic Abs and the noncatalytic Abs in detail. The catalytic Abs tended to have lower Kd for TSA1 and the short TSA2 than noncatalytic Abs. It was also observed that catalytic Abs showed clear enantiospecificity toward substrate 6 containing d-phenylalanine while noncatalytic Abs did not. The detailed analysis of kinetic and binding parameters for these antibodies gives us further insight into catalytic antibodies.

Animals↗
PubMed1999

Reliability of childhood mental disorder: diagnoses by Japanese psychologists.

The recent entry of psychologists into psychiatric practices and schools in Japan calls for diagnostic skills, because psychiatrists are less available in such settings. We examined the reliability of the diagnoses of 10 DSM-IV childhood mental disorders by 11 Japanese psychologists, using 20 case vignettes. Most categories had good reliability (kappa), except for attention deficit hyperactivity disorder. Japanese clinical psychologists may be able to use DSM-IV reliably as a tool for diagnosis of childhood psychiatric disorders, if sufficient training is provided.

Adolescent↗
PubMed1999

Changes in resistive index following extracorporeal shock wave lithotripsy.

BACKGROUND: Extracorporeal shock wave lithotripsy (ESWL) has replaced most surgical and endourologic forms of therapy for upper urinary tract stone disease. Despite its proved safety and efficacy, its adverse effects on renal function are still to be identified. A newer diagnostic technique, color Doppler ultrasonography, has brought a new insight into renal function. It enables precise evaluation of the renal vascular supply. Changes in intrarenal vascular resistance after ESWL were studied with Doppler ultrasound techniques. METHODS: In 70 consecutive patients the resistive index (RI) was measured at an interlober artery before and 30 min after ESWL in the treated and contralateral kidneys. In 17 patients, a follow-up Doppler study was performed 1 week after ESWL. RESULTS: In the treated kidneys, the RI significantly increased from 0.656+/-0.053 (mean +/- SD) at baseline to 0.682+/-0.053 (P<0.0001). There was no significant correlation of increase in RI with patient age (r = 0.010) or with pre-ESWL blood pressure (r = 0.002). Elderly patients (> or =60 years old, n = 31) had higher RI levels on baseline than younger patients (<60 years old, n = 39). In 18 of the 31 (58.1%) elderly cases the RI were elevated to greater than 0.7, indicating pathologic changes. In younger patients, only 9 (23.1%) experienced increase in RI up to 0.7 or greater. The contralateral untreated kidneys showed significant change in RI before (0.664+/-0.045) and after (0.679+/-0.049) lithotripsy in elderly patients (P<0.005). A follow-up Doppler study showed that the mean RI returned to pretreatment levels after 1 week. CONCLUSIONS: Because of higher RI levels on baseline, elderly patients have a higher risk of post-ESWL renal tissue damage than younger patients. Clinical implication of RI change in the contralateral kidneys in this study remains to be answered. The measurement of changes in RI with Doppler ultrasound techniques after ESWL may provide useful information for clinical diagnosis of renal tissue damage.

Adolescent↗